Roflumilast

Targets (4)

Identification

Name

Roflumilast

Accession Number

DB01656 (EXPT02802)

Type

Small Molecule

Groups

Approved

Description

Roflumilast is a phosphodiesterase-4 (PDE-4) inhibitor. Due to its selective inhibition of the PDE4 isoenzyme in lung cells, roflumilast is indicated for the management of chronic obstrtuctive pulmonary disease (COPD) exacerbations. Treatment with Roflumilast is associated with an increase in psychiatric adverse reactions, including suicide and suicidal attempts.

Pharmacology

Indication

Roflumilast is indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Roflumilast is not a bronchodilator and is not indicated for the relief of acute bronchospasm.

Roflumilast is a phosphodiesterase-4 (PDE-4) inhibitor which, due to its selective inhibition of the PDE4 isoenzyme, has potential antiinflammatory and antimodulatory effects in the pulmonary system. It is thought that the increased levels of intracellular cyclic AMP are responsible for the therapeutic actions of Roflumilast.

After a 500mcg dose, the bioavailability of roflumilast is about 80%. In the fasted state, maximum plasma concentrations are reached in 0.5 to 2 hours. While in the fed state, Cmax is reduced by 40%, Tmax is increased by one hour, and total absorption is unchanged.

Volume of distribution

Roflumilast has a Vd of 2.9L/kg with a dose of 500mcg. Permeability of roflumilast across the blood-brain barrier appears to be poor in rat studies.

Protein binding

Roflumilast is 99% plasma protein bound.

Metabolism

Roflumilast is metabolized to roflumilast N-oxide, the active metabolite of roflumilast in humans, by CYP3A4 and CYP1A2.